Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000213799 | SCV000275344 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-23 | criteria provided, single submitter | clinical testing | The p.K287M variant (also known as c.860A>T), located in coding exon 7 of the CHEK2 gene, results from an A to T substitution at nucleotide position 860. The lysine at codon 287 is replaced by methionine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000539843 | SCV000633225 | uncertain significance | Familial cancer of breast | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 287 of the CHEK2 protein (p.Lys287Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 231478). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Color Diagnostics, |
RCV000213799 | SCV000913992 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with methionine at codon 287 of the CHEK2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CHEK2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Gene |
RCV001575094 | SCV001802012 | uncertain significance | not provided | 2019-09-09 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; No data available from control populations to assess the frequency of this variant |
| Baylor Genetics | RCV000539843 | SCV004217628 | uncertain significance | Familial cancer of breast | 2023-07-20 | criteria provided, single submitter | clinical testing | |
| True Health Diagnostics | RCV000213799 | SCV000788005 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-09-29 | no assertion criteria provided | clinical testing |